Exploratory fMRI Study on the Treatment for Impulsive Aggression in Children With ADHD

Supernus Pharmaceuticals

Status and phase: Terminated; Phase 2

Conditions: Attention Deficit Hyperactivity Disorder (ADHD); Impulsive Aggression

Treatments: Diagnostic Test: Functional Magnetic Resonance Imaging (fMRI); Drug: SPN-810; Drug: Placebo; Diagnostic Test: Magnetic Resonance Spectroscopy (MRS); Behavioral: Point Subtraction Aggression Paradigm (PSAP) Task

Study type: Interventional

Funder types: Industry

Identifiers

NCT03638466

810P204

Details and patient eligibility

About

The purpose of this study was to evaluate the effect of 4-week SPN-810 treatment on brain functioning in patients aged 8-12 years with ADHD and associated feature of impulsive aggression (IA). This was achieved using functional magnetic resonance imaging (fMRI) in conjunction with the point subtraction aggression paradigm (PSAP) Task, a behavioral aggression paradigm in which subjects are provoked by having money indirectly taken from them by a fictitious opponent, simulating an aggression response.

Full description

Approximately 30 subjects aged 8-12 diagnosed with ADHD and associated feature of IA were recruited in this study. The PSAP is a behavioral aggression test used to evaluate behavioral response related to impulsive aggression. The task was combined with functional MRI to evaluate the change in brain activity measured as BOLD signal (blood oxygenation level-dependent) from baseline to the end of the treatment with SPN-810.

The level of neurotransmitters Glutamate and GABA were also measured using magnetic resonance spectroscopy (MRS).

Additionally, the improvement and severity in impulsive aggression behaviors were assessed using validated scales.

Enrollment: 7 patients

Sex: All

Ages: 8 to 12 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Otherwise healthy male or female subjects, aged 8-12 years, inclusive, at the time of screening with primary diagnosis of ADHD and currently receiving monotherapy treatment with an optimized US Food and Drug Administration (FDA)-approved ADHD medication.
• Impulsive aggression (IA) confirmed at screening using the R-MOAS and the Vitiello Aggression Scale.

Exclusion criteria

• Current or lifetime diagnosis of epilepsy, major depressive disorder, bipolar disorder, schizophrenia or related disorder, personality disorder, Tourette's disorder, fetal alcohol syndrome, or psychosis not otherwise specified.
• Currently meeting DSM criteria for autism spectrum disorder, pervasive developmental disorder, obsessive-compulsive disorder, post-traumatic stress disorder.
• Known or suspected IQ <70, pregnancy, substance or alcohol abuse.
• Known history of implanted brain stimulator, vagal nerve stimulator, ventriculoperitoneal shunt, cardiac pacemaker, orthodontic braces, or implanted medication port. Visual and hearing (≥25 dB) impairment.
• Pre-existing medical or psychological conditions that preclude being in the MRI scanner (e.g., claustrophobia, morbid obesity, or marked anxiety about the procedure).

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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7 participants in 2 patient groups, including a placebo group

High dose SPN-810 (36 mg)

Active Comparator group

Description:

Subjects were randomized to receive SPN-810 18 mg twice a day twice each day with and without food, in addition to the stable dose of the optimized ADHD medication.

Treatment:

Behavioral: Point Subtraction Aggression Paradigm (PSAP) Task

Diagnostic Test: Magnetic Resonance Spectroscopy (MRS)

Drug: SPN-810

Diagnostic Test: Functional Magnetic Resonance Imaging (fMRI)

Placebo

Placebo Comparator group

Description:

Subjects were randomized to receive Placebo twice a day twice each day with and without food, in addition to the stable dose of the optimized ADHD medication.

Treatment:

Behavioral: Point Subtraction Aggression Paradigm (PSAP) Task

Diagnostic Test: Magnetic Resonance Spectroscopy (MRS)

Drug: Placebo

Diagnostic Test: Functional Magnetic Resonance Imaging (fMRI)